3-183884463-C-T

Variant names:

• chr3-183884463-C-T
• rs12054027
• NM_018622.7:c.125+259G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018622.7(PARL):​c.125+259G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 152,082 control chromosomes in the GnomAD database, including 13,688 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.41 (13688 hom., cov: 33)
• Consequence: PARL NM_018622.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.533
• Publications: 4 publications found

Genes affected

PARL (HGNC:18253): (presenilin associated rhomboid like) This gene encodes a member of the rhomboid family of intramembrane serine proteases that is localized to the inner mitochondrial membrane. The encoded protein regulates mitochondrial remodeling and apoptosis through regulated substrate proteolysis. Proteolytic processing of the encoded protein results in the release of a small peptide, P-beta, which may transit to the nucleus. Mutations in this gene may be associated with Parkinson's disease. [provided by RefSeq, May 2016]

ENSG00000283765 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.477 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARL	NM_018622.7	c.125+259G>A		intron_variant	Intron 1 of 9	ENST00000317096.9	NP_061092.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PARL	ENST00000317096.9	c.125+259G>A		intron_variant	Intron 1 of 9	1	NM_018622.7	ENSP00000325421.5
ENSG00000283765	ENST00000639401.1	c.125+259G>A		intron_variant	Intron 1 of 10	5		ENSP00000491227.1

Frequencies

GnomAD3 genomes AF: 0.414 AC: 62962 AN: 151964 Hom.: 13692 Cov.: 33

Gnomad AFR AF: 0.289

Gnomad AMI AF: 0.299

Gnomad AMR AF: 0.481

Gnomad ASJ AF: 0.554

Gnomad EAS AF: 0.423

Gnomad SAS AF: 0.418

Gnomad FIN AF: 0.321

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.482

Gnomad OTH AF: 0.453

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.414 AC: 62961 AN: 152082 Hom.: 13688 Cov.: 33 AF XY: 0.408 AC XY: 30355 AN XY: 74326

African (AFR) AF: 0.289 AC: 11975 AN: 41470

American (AMR) AF: 0.481 AC: 7347 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.554 AC: 1922 AN: 3470

East Asian (EAS) AF: 0.423 AC: 2188 AN: 5170

South Asian (SAS) AF: 0.418 AC: 2017 AN: 4822

European-Finnish (FIN) AF: 0.321 AC: 3389 AN: 10560

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.482 AC: 32747 AN: 67990

Other (OTH) AF: 0.447 AC: 942 AN: 2108

Alfa AF: 0.438 Hom.: 1939

Bravo AF: 0.426

Asia WGS AF: 0.409 AC: 1426 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.8
DANN	Benign	0.77
PhyloP100		0.53
PromoterAI		0.0028	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs12054027; hg19: chr3-183602251; COSMIC: COSV57701577; COSMIC: COSV57701577;